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The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study

Research output: Contribution to journalArticle

Original languageEnglish
Article numberddy434
Pages (from-to)1322-1330
Number of pages9
JournalHuman Molecular Genetics
Issue number8
Early online date18 Dec 2018
DateAccepted/In press - 30 Nov 2018
DateE-pub ahead of print - 18 Dec 2018
DatePublished (current) - 15 Apr 2019


Given clear evidence that smoking lowers weight, it is possible that individuals with higher body mass index (BMI) smoke in order to lose or maintain their weight.

We performed Mendelian randomization (MR) analyses of the effects of BMI on smoking behaviour in UK Biobank and the Tobacco and Genetics consortium GWAS, on cotinine levels and nicotine metabolite ratio in published GWAS, and on DNA methylation in the Avon Longitudinal Study of Parents and Children.

Our results indicate that higher BMI causally influences lifetime smoking, smoking initiation , smoking heaviness and also DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) locus, but not smoking cessation. While there is no strong evidence that BMI causally influences cotinine levels, suggestive evidence for a negative causal influence on nicotine metabolite ratio may explain this.

There is a causal effect of BMI on smoking, but the relationship is likely to be complex due to opposing effects on behaviour and metabolism.

    Research areas

  • Nicotine, Smoking, body mass index procedure, metabolism, Genome-Wide Association Study, Mendelian randomisation analysis

    Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol
  • Physical and Mental Health

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